title: Afatinib for the treatment of patients with EGFR-positive non-small cell lung cancer.
abstract: Epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors (TKIs) are valuable treatments for EGFR-mutated non-small cell lung cancer (NSCLC). Anti-EGFR antibodies are widely used in the treatment of head and neck squamous cell carcinomas (HNSCC) and in KRAS wild-type colorectal cancer. The first-generation, reversible EGFR inhibitors erlotinib and gefitinib in the first-line setting provide superior progression-free survival and quality of life compared to conventional chemotherapy in NSCLC harboring activating EGFR mutations. However, these therapies eventually fail and new options are needed. Afatinib is a novel irreversible inhibitor of the ErbB family members EGFR, tyrosine kinase-type cell surface receptors HER2 and HER4. It shows preclinical efficacy in NSCLC with common EGFR-activating mutations and the T790M mutation typically associated with EGFR TKI resistance. Preclinical activity is seen in other tumor types as well, including HNSCC. Clinically, afatinib has been evaluated in the broad-reaching LUX Lung trial program, with significant activity seen in the first and later-line settings. It is also under investigation in multiple other tumor types. This review will stress on afatinib's preclinical pharmacology, pharmacokinetics and clinical activity with a focus on NSCLC.
authors.affiliation: University of Colorado School of Medicine, Division of Medical Oncology, and Denver Veterans Affairs Medical Center, Denver, Colorado, USA. antonio.jimeno@ucdenver.edu.
authors.forename: D W
authors.initials: DW
authors.lastname: Bowles
authors.forename: A
authors.initials: A
authors.lastname: Weickhardt
authors.forename: A
authors.initials: A
authors.lastname: Jimeno
mesh_terms: D000077716:Afatinib; D000818:Animals; D000970:Antineoplastic Agents / Q000009:adverse effects / Q000494:pharmacology / Q000627:therapeutic use; D002289:Carcinoma, Non-Small-Cell Lung / Q000188:drug therapy* / Q000235:genetics; D004353:Drug Evaluation, Preclinical; D004347:Drug Interactions; D019008:Drug Resistance, Neoplasm; D066246:ErbB Receptors / Q000235:genetics; D006801:Humans; D008175:Lung Neoplasms / Q000188:drug therapy* / Q000235:genetics; D011788:Quality of Life; D011799:Quinazolines / Q000009:adverse effects / Q000494:pharmacology / Q000627:therapeutic use*
chemical_list: D000970:Antineoplastic Agents; D011799:Quinazolines; D000077716:Afatinib; D066246:ErbB Receptors
keywords: Afatinib; BIBW-2992; Dual inhibitor; EGFR; Non-small cell lung cancer